Firefly Gene Lights the Way for St. Thomas Toxicologist

Kelly Engebretson '99 M.A.

2 years ago

Dalma Martinovic-Weigelt, Ph.D., St. Thomas Biology Department faculty member and director of the Environmental Science program, has focused her career on endocrine-disrupting chemicals, and other chemicals of emerging concern, in aquatic environments. The objective? To develop approaches to evaluate whether these chemicals present threats to ecological and human health. While labs provide her with pristine, idyllic settings to conduct some of her studies, she is more likely to be found in the field researching urban streams and wastewater.

Martinovic-Weigelt has studied contaminants in Minnesota waters for more than 10 years. Many of her studies of late have taken a twist with an innovative and beguiling tool: a breast cancer cell genetically modified with a firefly gene. She exposes the cells to a water sample and waits for a reaction – or not. If estrogens are present, the cells will light up thanks to luciferase, the enzyme in fireflies that sets them alight. Most recently she used the cell to analyze samples from 10 Minnesota rivers.

The science behind the cell

In general, breast cancer cells are useful in scientific studies because they naturally express a receptor for estrogens, which means estrogens – whether natural or synthetic – can easily bind to them. Among the thousands of types of estrogens in existence, many are good – like those that occur naturally in our bodies and are responsible for reproductive health, as well as those that occur naturally in the environment in fish and plants. The “bad” estrogens, which Martinovic-Weigelt’s research looks for, are xenoestrogens, chemicals that mimic estrogens. These contaminants often find their way into lakes by way of wastewater plants, which filter most but not all of the chemicals.

The problem with estrogens is that even at very little concentrations, they have a biological effect on organisms, either blocking or activating cells. For example, published studies have shown that these chemicals can feminize male fish, a consequence that lessens their chances of finding a mate and can even take away their ability to reproduce.

“We (scientists) often say estrogen receptors are promiscuous. As it turns out, they haven’t evolved to be very selective, so their structure is such that they will bind to a lot of different chemicals,” she said. That’s why toxicologists are keeping a close on eye them.

Martinovic-Weigelt’s firefly study of Minnesota rivers detected a number of estrogenic contaminants, including breakdown products of household detergents, such as alkylphenols; antimicrobial agents, such as triclosan, which is found in many soaps, clothing and even toys; and Bisphenol A, or BPA, an estrogenic chemical used in the manufacture of polycarbonate plastic.

The results from Martinovic-Weigelt’s ongoing “firefly project” will help scientists prioritize the risk of contaminants found in her aquatic samples from across Minnesota – taken from the Knife River in northern part of the state and the Zumbro River to the south, among others. She also has analyzed Minnesota lakes for around 200 types of chemicals that could be hiding in the water but does not have data from those studies yet.

A ‘crazy and amazing’ path to public health

“As a toxicologist, I’m interested in how contaminants in the environment impact aquatic life primarily, but I’ve been shifting a bit more toward global health and water quality. My fish research indirectly involves public health because it informs those decisions,” Martinovic-Weigelt said. “I’ve also been trying to help enrich the curriculum in the Biology Department’s global health program, which we started two years ago.”

Of the thousands of chemicals currently in commerce, only a small percentage are regulated, and there often is minimal testing on those that are. Ultimately this research aims to close that gap by generating as much data as possible on as many chemicals as possible.

“A lot of these chemicals that are in, for example, the cosmetics and household cleaners we use are not regulated, so we are using them without really knowing if they might be bad for us,” she said. “They aren’t regulated because we don’t know much about them and yet they’re allowed to go on the market. That’s why this technology is so important. There needs to be a little fear about this stuff.”

Martinovic-Weigelt described the technological advance, whose formal name is T47-KB LUC, as “a crazy system, and amazing.” The hybrid cell has been around “a little while” and was invented by another scientist, but what makes her study unique is her use of the cell to analyze the water samples.

“We can figure out the concentrations of chemicals, but we can’t know for sure how they got there, and we know even less about what they do. One chemical can do so many different things, so it can be very hard for us to estimate the biological risk they might pose,” she said.

But “very hard” is far from impossible. This is where the United States’ Environmental Protection Agency and the National Institutes of Health come into play. The two organizations, which have been assisting Martinovic-Weigelt’s firefly research for several years, provide access to expensive robots that can generate hundreds of types of chemical data from her samples in a dizzyingly short amount of time. Armed with this data, she and her collaborators, St. Thomas faculty Kerri Carlson, Ph.D. (Biology Department), and Erin Curran, Ph.D. (Computer and Information Sciences Department, are better equipped to delve into their areas of expertise, and their imaginations, to connect which chemicals might be responsible for which effects.

The other novelty in her research – this particular type of cell also has been used in many unrelated studies, including medical studies – is that the human health and ecological health communities typically have no interaction, according to Martinovic-Weigelt.

“Fortunately, in Minnesota, we understand how both areas are interconnected; our state agencies [namely the Minnesota Pollution Control Agency, under which Martinovic-Weigelt studies, and the Minnesota Department of Health], work together, and I am one of the people involved in those conversations,” she said.

Martinovic-Weigelt’s firefly studies are funded, in part, by a National Science Foundation grant. In addition to Carlson and Curran, she has collaborated with numerous colleges and universities and environmental agencies and departments, including Minnesota Pollution Control Agency, Minnesota Department of Health, the EPA, U.S. Geological Survey and even the U.S. Army, as well as with undergraduate students Abigail Lukowicz and Nicholas Cipoletti ’15, who won a national award for best undergraduate student presentation at the annual meeting of Society of Environmental Toxicology and Chemistry in November.